1. MUTATIONS IN DSTYK AND DOMINANT
URINARY TRACT MALFORMATIONS
C a r o l i n a C a r v a j a l M i r a n d a
C h r i s t i a n S á n c h e z v a l e n c i a
U P B - F a c u l t a d d e M e d i c i n a
M e d e l l í n
S. Sanna-Cherchi, R.V. Sampogna, N. Papeta, K.E. Burgess, S.N. Nees, B.J. Perry,
M. Choi, M. Bodria, Y. Liu, P.L. Weng, V.J. Lozanovski, M. Verbitsky, F. Lugani,
R. Sterken, N. Paragas, G. Caridi, A. Carrea, M. Dagnino, A. Materna-Kiryluk,
G. Santamaria, C. Murtas, N. Ristoska-Bojkovska, C. Izzi, N. Kacak, B. Bianco,
S. Giberti, M. Gigante, G. Piaggio, L. Gesualdo, D. Kosuljandic Vukic,
K. Vukojevic, M. Saraga-Babic, M. Saraga, Z. Gucev, L. Allegri, A. Latos-Bielenska,
D. Casu, M. State, F. Scolari, R. Ravazzolo, K. Kiryluk, Q. Al-Awqati, V.D. D’Agati,
I.A. Drummond, V. Tasic, R.P. Lifton, G.M. Ghiggeri, and A.G. Gharavi

2. Introducción

3. Urinary malformation: Alteration of
the shape of the organs in the
urinary tract caused by a
development desorder.
23% of birth defects.
40-50% pediatric,7% of adult
cases(ESRD)

5. URINARY TRACT MALFORMATIONS
Kidney
o Renal agenesis:
Unilateral, Kidney is either absent or
undeveloped.
o Renal hypoplasia:
Small kidney with the other one larger than
normal
o Renal dysplasia and multicystic kidney:
Normally only one kidney irregularly
lobulated mass of cysts.
o Ectopic kidney:
Not ascend properly.

6. URINARY TRACT MALFORMATIONS
Ureter and ureteropelvic junction
Ureteral atresia:
Ureter may be absent or fail to extend to the
bladder
Duplication of the ureter:
Most common,recurrent urinary tract
infections.
Obstructed mega-ureter:
Obstruction at the ureterovesical junction.

7. URINARY TRACT MALFORMATIONS
Bladder
Bladder exstrophy:
Absence of the anterior wall of the
bladder, with ureters delivering urine
into the lower abdomen.
Persistent urachus:
Draining umbilical sinus and can
become infected.
Contracture of the bladder neck:
Causes reflux, bladder diverticula and
irritable bladder.

8. MUTATIONS IN DSTYK
This gene encodes a dual serine/threonine
and tyrosine protein kinase which is
expressed in multiple tissues. It is thought to
function as a regulator of cell death.

9. DSTYK
kinase
ERK FGF-induced
transcriptional activity
MALFORMATION
FG2

10. Objetivo

11. Identify independent mutations in DSTYK in
patients with congenital abnormalities of the
kidney and urinary tract.

12. Materiales y métodos

13. Genotipificacion:determina genotipo. Diferencias
en movilidad de los fragmentos de ADN en
geles, amplificación diferencial por PCR, o la
hibridación.
Secuenciacion:determinación del orden de los
nucleótidos en un oligonucleótido de ADN.

14. Inmortalizacion de linfocitos: cultivos proliferación
ilimitada + células mas renovación, mediante
transformación por tto químico o una infección
viral.
 17 Miembros familiares

15. Inmunohistoquimica: uso de anticuerpo , marcado
enzima (sut. Visible) Test: ratones,1 riñon(3meces)
Inmunofluorescencia:anti-RIPS,FGF (Factor de Cto
fibroblastico) FGF1,2,anti-acuaporina 2, anti-E-
Cadherina

16. Pez Zebra Knock down: modificacion para expresión
reducida de genes insertando pequeños fragmentos
u oligonucleótido con secuencia complementaria.
Morpholino------Bloquea DSTYK

17. Western blot: detectar proteínas específicas en una
muestra determinada

18. Resultados

30. Discussion

31. Reference What they said? Agree /
Desagree
Schedl A.
“The development of the kidney and the urinary tract
is orchestrated by a series of inductive signals between
the metanephric mesenchyme and the ureteric bud,
and any disruption of this reciprocal signaling results in
developmental defects”.

Sanna-
Cherchi S et al
“The diversity of signaling pathways in nephrogenesis
explains the significant locus heterogeneity of
congenital abnormalities of the kidney and urinary
tract”.

Bates CM.
“Different combinations of FGF ligands are expressed
in the ureteric bud, metanephric mesenchyme, and
renal stroma”. 
Guillemot F et
al
Engagement of the FGF receptor results in
autophosphorylation and activation of the intracellular
mitogen-activated protein kinase cascade, ultimately
resulting in the production of pERK, the main effector
of the FGF transcriptional program.


32. Conclusions

33. Its very important to know the changes that can
happen to DSTYK gene because helps to diagnose
abnormalities of the kidney and urinary tract.
The exome sequencing is an important tool for
diagnosis in patients with genetic pathologies
heterogeneous.
The loss of fibroblast growth factor FGF and
developmental defects in multiple organs is
indicative of the presence of gene DSTYK.
Any alteration in the signaling process that induces
renal embryonic tissue develops has as results
pathological defect in the formation of this organ
and routes of excretion.
1
2
3
4

34. Mapas
conceptuales